Calixarenes (CAs), representing the third generation of supramolecular hosts and one of the most widely studied macrocyclic scaffolds, offer (almost) unlimited structure and application possibilities ...due to their ease of modification, which allows one to establish a large molecular library as a material basis for diverse biomedical applications. Moreover, CAs and their derivatives engage in various noncovalent interactions for the facile recognition of guests including bioactive molecules and are also important building blocks for the fabrication of supramolecular architectures. In view of their molecular recognition and self‐assembly properties, CAs are extensively applied in biosensing, bioimaging, and drug/gene delivery. Additionally, some CA derivatives exhibit biological activities and can therefore be used as new therapeutic agents. Herein, we summarize the diverse biomedical applications of CAs including in vitro diagnosis (biosensing), in vivo diagnosis (bioimaging), and therapy.
Calixarenes (CAs) represent the third generation of supramolecular hosts and one of the most widely studied macrocyclic scaffolds. They offer almost unlimited structural possibilities due to their ease of modification, providing a tremendous molecular library as a material basis for diverse biomedical applications.
Reported herein are two new polymorphic Co‐MOFs (CTGU‐5 and ‐6) that can be selectively crystallized into the pure 2D or 3D net using an anionic or neutral surfactant, respectively. Each polymorph ...contains a H2O molecule, but differs dramatically in its bonding to the framework, which in turn affects the crystal structure and electrocatalytic performance for hydrogen evolution reaction (HER). Both experimental and computational studies find that 2D CTGU‐5 which has coordinates water and more open access to the cobalt site has higher electrocatalytic activity than CTGU‐6 with the lattice water. The integration with co‐catalysts, such as acetylene black (AB) leads to a composite material, AB&CTGU‐5 (1:4) with very efficient HER catalytic properties among reported MOFs. It exhibits superior HER properties including a very positive onset potential of 18 mV, low Tafel slope of 45 mV dec−1, higher exchange current density of 8.6×10−4 A cm−2, and long‐term stability.
HER choice of surfactants: Two new Co‐MOFs phase‐selected by anionic and neutral surfactants exhibit differential affinity for entrapped water molecules, leading to a difference in the spatial accessibility of active metal sites. A composite material made from such Co‐MOFs shows impressive performance in electrocatalytic hydrogen evolution reaction (HER) as well as long‐term stability.
The integration of heterometallic units and nanostructures into metal–organic frameworks (MOFs) used for the oxygen evolution reaction (OER) can enhance the electrocatalytic performance and help ...elucidate underlying mechanisms. We have synthesized a series of stable MOFs (CTGU‐10a1–d1) based on trinuclear metal carboxylate clusters and a hexadentate carboxylate ligand with a (6,6)‐connected nia net. We also present a strategy to synthesize hierarchical bimetallic MOF nanostructures (CTGU‐10a2–d2). Among these, CTGU‐10c2 is the best material for the OER, with an overpotential of 240 mV at a current density of 10 mA cm−2 and a Tafel slope of 58 mV dec−1. This is superior to RuO2 and confirms CTGU‐10c2 as one of the few known high‐performing pure‐phase MOF‐OER electrocatalysts. Notably, bimetallic CTGU‐10b2 and c2 show an improved OER activity over monometallic CTGU‐10a2 and d2. Both DFT and experiments show that the remarkable OER performance of CTGU‐10c2 is due to the presence of unsaturated metal sites, a hierarchical nanobelt architecture, and the Ni–Co coupling effect.
Finding the right balance: The integration of heterometallic clusters and nanostructures into stable hierarchical nanosheet‐based bimetal–organic frameworks allows to increase the oxygen evolution reaction performance of electrocatalysts. The ideal ratio between Co and Ni leads to one of the best performances of pure‐phase MOF–OER electrocatalysts.
Embedding cubane M4(OH)4 (M=Ni, Co) clusters within the matrix of metal–organic frameworks (MOFs) is a strategy to develop materials with unprecedented synergistic properties. Herein, a new material ...type based on the pore‐space partition of the cubic primitive minimal‐surface net (MOF‐14‐type) has been realized. CTGU‐15 made from the Ni4(OH)4 cluster not only has very high BET surface area (3537 m2 g−1), but also exhibits bi‐microporous features with well‐defined micropores at 0.86 nm and 1.51 nm. Furthermore, CTGU‐15 is stable even under high pH (0.1 m KOH), making it well suited for methanol oxidation in basic medium. The optimal hybrid catalyst KB&CTGU‐15 (1:2) made from ketjen black (KB) and CTGU‐15 exhibits an outstanding performance with a high mass specific peak current of 527 mA mg−1 and excellent peak current density (29.8 mA cm−2) at low potential (0.6 V). The isostructural cobalt structure (CTGU‐16) has also been synthesized, further expanding the application potential of this material type.
Split pores: A new 3D microporous metal–organic framework containing cubane Ni4(OH)4 clusters can serve as an electrocatalyst for the methanol oxidation reaction (MOR). The optimal hybrid material shows impressive electrocatalytic performance including a high mass specific peak current of 527 mA mg−1 and excellent peak current density (29.8 mA cm−2) at a very low potential (0.6 V).
Excess accumulation of amyloid‐β (Aβ) protein in the brain is the primary pathogenesis of Alzheimer's disease (AD). Inhibition of Aβ fibrillation and disaggregation of Aβ fibrils is an attractive ...therapeutic and preventive strategy for Aβ‐induced AD. Here, near infrared (NIR) light‐responsive nanoparticles (NPs) composed of amphiphilic guanidinocalix5arene (GC5A), 4‐(dodecyloxy)benzamido‐terminated methoxy poly(ethylene glycol), and photothermal conjugated polymer PDPP are fabricated. The NIR light‐responsive NPs can efficiently penetrate the blood‐brain barrier (BBB), inhibit amyloid‐β 42 (Aβ42) fibrillation, and disaggregate fibrils after NIR light irradiation. Through the advantage of containing GC5A, the NPs exhibit extremely strong binding affinity for the Aβ42 protein. Interestingly, upon NIR light irradiation, benefiting from the high photothermal conversion efficiency of PDPP, NPs generate local heat and effectively promote the BBB permeability. Moreover, NPs are multifunctional platforms for the inhibition of Aβ42 fibrillation and disaggregation of fibrils after irradiation with NIR light, distinctly reducing cytotoxicity and eliminating Aβ42 plaques in the hippocampus of AD mice. Hence, NPs provide an interesting strategy for the inhibition and disaggregation of Aβ42 fibrillation and present an excellent therapeutic strategy for amyloidosis.
The near infrared (NIR) light‐responsive nanoparticles (NPs) composed of calixarene (GC5A), and a conjugated polymer (PDPP) exhibit efficient permeability through the blood‐brain barrier and inhibit and disaggregate Aβ42 fibrillation. Upon NIR light irradiation, the NPs generate local heat and efficiently disaggregate Aβ42 fibrils, leading to the cytotoxicity of Aβ42 fibrils reduce, and eliminate Aβ42 plaques in Alzheimer's disease mouse brain.
With ever‐increasing energy consumption and continuous rise in atmospheric CO2 concentration, electrochemical reduction of CO2 into chemicals/fuels is becoming a promising yet challenging solution. ...Sn‐based materials are identified as attractive electrocatalysts for the CO2 reduction reaction (CO2RR) to formate but suffer from insufficient selectivity and activity, especially at large cathodic current densities. Herein, we demonstrate that Cu‐doped SnS2 nanoflowers can undergo in situ dynamic restructuring to generate catalytically active S‐doped Cu/Sn alloy for highly selective electrochemical CO2RR to formate over a wide potential window. Theoretical thermodynamic analysis of reaction energetics indicates that the optimal electronic structure of the Sn active site can be regulated by both S‐doping and Cu‐alloying to favor formate formation, while the CO and H2 pathways will be suppressed. Our findings provide a rational strategy for electronic modulation of metal active site(s) for the design of active and selective electrocatalysts towards CO2RR.
Sn‐based materials have been extensively explored in the electrochemical CO2 reduction reaction to formate, but reaching high selectivity and durability at large current densities remains challenging. Here, a catalytically active S‐doped Cu/Sn alloy was formed in situ through dynamic restructuring of Cu‐doped SnS2 nanoflowers, leading to an excellent CO2 to formate performance over a wide potential window.
Identification of grain shape determining genes can facilitate breeding of rice cultivars with optimal grain shape and appearance quality. Here, we identify GS9 (Grain Shape Gene on Chromosome 9) ...gene by map-based cloning. The gs9 null mutant has slender grains, while overexpression GS9 results in round grains. GS9 encodes a protein without known conserved functional domain. It regulates grain shape by altering cell division. The interaction of GS9 and ovate family proteins OsOFP14 and OsOFP8 is modulated by OsGSK2 kinase, a key regulator of the brassinosteroids signaling pathway. Genetic interaction analysis reveals that GS9 functions independently from other previously identified grain size genes. Introducing the gs9 allele into elite rice cultivars significantly improves grain shape and appearance quality. It suggests potential application of gs9, alone or in combination with other grain size determining genes, in breeding of rice varieties with optimized grain shape.
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that belongs to the phosphoinositide 3-kinase (PI3K)-related kinase (PIKK) family. The kinase exists in the forms of two ...complexes, mTORC1 and mTORC2, and it participates in cell growth, proliferation, metabolism, and survival. The kinase activity is closely related to the occurrence and development of multiple human diseases. Inhibitors of mTOR block critical pathways to produce antiviral, anti-inflammatory, antiproliferative and other effects, and they have been applied to research in cancer, inflammation, central nervous system diseases and viral infections. Existing mTOR inhibitors are commonly divided into mTOR allosteric inhibitors, ATP-competitive inhibitors and dual binding site inhibitors, according to their sites of action. In addition, there exist several dual-target mTOR inhibitors that target PI3K, histone deacetylases (HDAC) or ataxia telangiectasia mutated and Rad-3 related (ATR) kinases. This review focuses on the structure of mTOR protein and related signaling pathways as well as the structure and characteristics of various mTOR inhibitors. Non-rapalog allosteric inhibitors will open new directions for the development of new therapeutics specifically targeting mTORC1. The applications of ATP-competitive inhibitors in central nervous system diseases, viral infections and inflammation have laid the foundation for expanding the indications of mTOR inhibitors. Both dual-binding site inhibitors and dual-target inhibitors are beneficial in overcoming mTOR inhibitor resistance.
Exploring novel multifunctional rare earth materials is very important because these materials have fundamental interests, such as new structural facts and connecting modes, as well as potential ...technological applications, including optics, magnetic properties, sorption, and catalytic behaviors. Especially, employing these nanomaterials for sensing or catalytic reactions is still very challenging. Herein, a new superstable, anionic terbium‐metal–organic‐framework, H2N(CH3)2Tb(cppa)2(H2O)2, (China Three Gorges University (CTGU‐1), H2cppa = 5‐(4‐carboxyphenyl)picolinic acid), is successfully prepared, which can be used as a turn‐on, highly‐sensitive fluorescent sensor to detect Eu3+ and Dy3+, with a detection limitation of 5 × 10−8 and 1 × 10−4m in dimethylformamide, respectively. This result represents the first example of lanthanide‐metal–organic‐frameworks (Ln‐MOF) that can be employed as a discriminative fluorescent probe to recognize Eu3+ and Dy3+. In addition, through ion exchanging at room temperature, Ag(I) can be readily reduced in situ and embedded in the anionic framework, which leads to the formation of nanometal‐particle@Ln‐MOF composite with uniform size and distribution. The as‐prepared Ag@CTGU‐1 shows remarkable catalytic performance to reduce 4‐nitrophenol, with a reduction rate constant κ as large as 2.57 × 10−2 s−1; almost the highest value among all reported noble‐metal‐nanoparticle@MOF composites.
A new porous, anionic Tb‐metal–organic‐framework, China Three Gorges University (CTGU‐1), can serve as a turn‐on sensor for detection of Eu3+ and Dy3+, with different detection limits. Additionally, spontaneous in situ reduction and immobilization of ion‐exchanged Ag(I) to Ag nanoparticles in the anionic framework result in an Ag@CTGU‐1 composite, which can remarkably catalyze the reduction of 4‐nitrophenol.
The imbalance of amyloid‐β (Aβ) production and clearance causes aggregation of Aβ1‐42 monomers to form fibrils and amyloid plaques, which is an indispensable process in the pathogenesis of ...Alzheimer's disease (AD), and eventually leads to pathological changes and cognitive impairment. Consequently, Aβ1‐42 is the most important target for the treatment of AD. However, developing a single treatment method that can recognize Aβ1‐42, inhibit Aβ1‐42 fibrillation, eliminate amyloid plaques, improve cognitive impairments, and alleviate AD‐like pathology is challenging. Here, a coassembly composed of cyclodextrin (CD) and calixarene (CA) is designed, and it is used as an anti‐Aβ therapy agent. The CD–CA coassembly is based on the previously reported heteromultivalent recognition strategy and is able to successfully eliminate amyloid plaques and degrade Aβ1‐42 monomers in 5xFAD mice. More importantly, the coassembly improves recognition and spatial cognition deficits, and synaptic plasticity impairment in the 5xFAD mice. In addition, the coassembly ameliorates AD‐like pathology including prevention of neuronal apoptosis and oxidant stress, and alteration of M1/M2 microglial polarization states. This supramolecular approach makes full use of both molecular recognition and self‐assembly of macrocyclic amphiphiles, and is a promising novel strategy for AD treatment.
A heteromultivalent coassembly composed of cyclodextrin and calixarene (CD–CA coassembly) according to the composition of amino acids in Aβ1‐42 effectively recognizes and disaggregates Aβ1‐42 fibrils. Intranasal administration of the CD–CA coassembly eliminates amyloid plaque and neurodegeneration in the brain, and improves cognitive deficits in 5xFAD mice. This supramolecular approach is a promising novel strategy for treatment of Alzheimer's disease (AD).
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